{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:35:20Z","timestamp":1765546520628,"version":"3.37.3"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Hypermethylation of gene promoters has been regarded as an epigenetic regulator for gene inactivation in the development of several diseases. In the current study, we aimed to explore how long noncoding RNA X-inactive specific transcript (lncRNA XIST) function in collagen degradation in chondrocytes of osteoarthritis (OA) after tibial plateau fracture by regulating tissue inhibitor of metalloproteinase-3 (TIMP-3) promoter methylation.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>In silico analysis was used to screen differentially expressed lncRNAs in cartilage tissues of OA. Chondrocytes were then successfully isolated from normal and OA cartilage tissues and identified, with the expressions of lncRNA XIST and TIMP-3 examined. The methylation levels of TIMP-3 promoter were determined by MS-PCR. The binding of lncRNA XIST to DNA methyltransferase and the binding of TIMP-3 promoter to DNA methyltransferase were determined by a series of experiments, including RIP, RNA pull-down, and ChIP assays.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The differentially expressed lncRNA XIST was determined in OA. In addition, cartilage tissues of OA showed upregulation of lncRNA XIST and downregulation of TIMP-3. LncRNA XIST was primarily localized in the nucleus and was capable of binding to the promoter of TIMP-3. The silencing of lncRNA XIST decreased the methylation levels of TIMP-3 promoter and increased the expressions of TIMP-3, which consequently inhibited collagen degradation in OA chondrocytes. Furthermore, TIMP-3 over-expression reversed the effect of lncRNA XIST on collagen degradation in OA chondrocytes.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Collectively, lncRNA XIST raises collagen degradation in OA chondrocytes after tibial plateau fracture by accelerating the methylation of TIMP-3 promoter by recruiting DNA methyltransferase.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13075-019-2033-5","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T14:03:00Z","timestamp":1575900180000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Long non-coding XIST raises methylation of TIMP-3 promoter to regulate collagen degradation in osteoarthritic chondrocytes after tibial plateau fracture"],"prefix":"10.1186","volume":"21","author":[{"given":"Hongwei","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengdi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3481-6502","authenticated-orcid":false,"given":"Ruyi","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"issue":"Suppl 3","key":"2033_CR1","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.1097\/BOT.0000000000000892","volume":"31","author":"KA Egol","year":"2017","unstructured":"Egol KA, Cantlon M, Fisher N, Broder K, Reisgo A. Percutaneous repair of a Schatzker III tibial plateau fracture assisted by arthroscopy. J Orthop Trauma. 2017;31(Suppl 3):S12\u2013S3.","journal-title":"J Orthop Trauma"},{"key":"2033_CR2","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1016\/S0140-6736(16)31678-6","volume":"388","author":"GBD Disease","year":"2016","unstructured":"Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1545\u2013602.","journal-title":"Lancet."},{"key":"2033_CR3","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1002\/jor.21261","volume":"29","author":"TL Huang","year":"2011","unstructured":"Huang TL, Hsu HC, Yang KC, Lin FH. Hyaluronan up-regulates IL-10 expression in fibroblast-like synoviocytes from patients with tibia plateau fracture. J Orthopaedic Res. 2011;29:495\u2013500.","journal-title":"J Orthopaedic Res"},{"key":"2033_CR4","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/nrrheum.2016.136","volume":"12","author":"WH Robinson","year":"2016","unstructured":"Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016;12:580\u201392.","journal-title":"Nat Rev Rheumatol"},{"key":"2033_CR5","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1111\/jpi.12362","volume":"61","author":"A Hosseinzadeh","year":"2016","unstructured":"Hosseinzadeh A, Kamrava SK, Joghataei MT, Darabi R, Shakeri-Zadeh A, Shahriari M, et al. Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin. J Pineal Res. 2016;61:411\u201325.","journal-title":"J Pineal Res"},{"key":"2033_CR6","first-page":"595273","volume":"2015","author":"H Cho","year":"2015","unstructured":"Cho H, Walker A, Williams J, Hasty KA. Study of osteoarthritis treatment with anti-inflammatory drugs: cyclooxygenase-2 inhibitor and steroids. Biomed Res Int. 2015;2015:595273.","journal-title":"Biomed Res Int"},{"key":"2033_CR7","doi-asserted-by":"publisher","first-page":"489638","DOI":"10.1155\/2012\/489638","volume":"2012","author":"S Gallo","year":"2012","unstructured":"Gallo S, Karligkiotis A, Lenzi R, Castelnuovo P, Dallan I. Necrotizing craniocervical soft tissue infections: clinical experience and personal considerations. Case Reports Otolaryngol. 2012;2012:489638.","journal-title":"Case Reports Otolaryngol"},{"key":"2033_CR8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.joca.2012.11.012","volume":"21","author":"F Berenbaum","year":"2013","unstructured":"Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013;21:16\u201321.","journal-title":"Osteoarthr Cartil"},{"key":"2033_CR9","doi-asserted-by":"publisher","first-page":"941","DOI":"10.3892\/or.2017.5751","volume":"38","author":"Y Tang","year":"2017","unstructured":"Tang Y, He R, An J, Deng P, Huang L, Yang W. lncRNA XIST interacts with miR-140 to modulate lung cancer growth by targeting iASPP. Oncol Rep. 2017;38:941\u20138.","journal-title":"Oncol Rep"},{"key":"2033_CR10","doi-asserted-by":"publisher","first-page":"3595","DOI":"10.1096\/fj.14-260323","volume":"29","author":"JL Marques-Rocha","year":"2015","unstructured":"Marques-Rocha JL, Samblas M, Milagro FI, Bressan J, Martinez JA, Marti A. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J. 2015;29:3595\u2013611.","journal-title":"FASEB J"},{"key":"2033_CR11","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1002\/art.38309","volume":"66","author":"Q Liu","year":"2014","unstructured":"Liu Q, Zhang X, Dai L, Hu X, Zhu J, Li L, et al. Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis. Arthritis Rheumatol. 2014;66:969\u201378.","journal-title":"Arthritis Rheumatol"},{"key":"2033_CR12","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1016\/j.bbrc.2018.07.015","volume":"503","author":"L Li","year":"2018","unstructured":"Li L, Lv G, Wang B, Kuang L. The role of lncRNA XIST\/miR-211 axis in modulating the proliferation and apoptosis of osteoarthritis chondrocytes through CXCR4 and MAPK signaling. Biochem Biophys Res Commun. 2018;503:2555\u201362.","journal-title":"Biochem Biophys Res Commun"},{"key":"2033_CR13","first-page":"5828","volume":"22","author":"HX Zhang","year":"2018","unstructured":"Zhang HX, Sun C, Yu HC, Song B, Pan ZX. Targeted inhibition of beta-catenin by miR-320 and decreased MMP-13 expression in suppressing chondrocyte collagen degradation. Eur Rev Med Pharmacol Sci. 2018;22:5828\u201335.","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2033_CR14","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1593\/neo.08208","volume":"10","author":"P Gu","year":"2008","unstructured":"Gu P, Xing X, Tanzer M, Rocken C, Weichert W, Ivanauskas A, et al. Frequent loss of TIMP-3 expression in progression of esophageal and gastric adenocarcinomas. Neoplasia. 2008;10:563\u201372.","journal-title":"Neoplasia."},{"key":"2033_CR15","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.archoralbio.2014.02.016","volume":"59","author":"W Li","year":"2014","unstructured":"Li W, Wu M, Jiang S, Ding W, Luo Q, Shi J. Expression of ADAMTs-5 and TIMP-3 in the condylar cartilage of rats induced by experimentally created osteoarthritis. Arch Oral Biol. 2014;59:524\u20139.","journal-title":"Arch Oral Biol"},{"key":"2033_CR16","doi-asserted-by":"publisher","first-page":"7771","DOI":"10.1038\/s41598-017-08418-8","volume":"7","author":"A Takahashi","year":"2017","unstructured":"Takahashi A, de Andres MC, Hashimoto K, Itoi E, Otero M, Goldring MB, et al. DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes. Sci Rep. 2017;7:7771.","journal-title":"Sci Rep"},{"key":"2033_CR17","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1186\/s13075-017-1454-2","volume":"19","author":"H Li","year":"2017","unstructured":"Li H, Wang D, Yuan Y, Min J. New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Res Ther. 2017;19:248.","journal-title":"Arthritis Res Ther."},{"key":"2033_CR18","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1002\/art.39643","volume":"68","author":"O Alvarez-Garcia","year":"2016","unstructured":"Alvarez-Garcia O, Fisch KM, Wineinger NE, Akagi R, Saito M, Sasho T, et al. Increased DNA methylation and reduced expression of transcription factors in human osteoarthritis cartilage. Arthritis Rheumatol. 2016;68:1876\u201386.","journal-title":"Arthritis Rheumatol"},{"key":"2033_CR19","doi-asserted-by":"publisher","first-page":"R190","DOI":"10.1186\/ar4380","volume":"15","author":"CH Chou","year":"2013","unstructured":"Chou CH, Wu CC, Song IW, Chuang HP, Lu LS, Chang JH, et al. Genome-wide expression profiles of subchondral bone in osteoarthritis. Arthritis Res Ther. 2013;15:R190.","journal-title":"Arthritis Res Ther"},{"key":"2033_CR20","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47.","journal-title":"Nucleic Acids Res"},{"key":"2033_CR21","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.3892\/etm.2015.2434","volume":"9","author":"C Cheng","year":"2015","unstructured":"Cheng C, Zhang FJ, Tian J, Tu M, Xiong YL, Luo W, et al. Osteopontin inhibits HIF-2alpha mRNA expression in osteoarthritic chondrocytes. Exp Therapeutic Med. 2015;9:2415\u20139.","journal-title":"Exp Therapeutic Med"},{"key":"2033_CR22","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.jphotobiol.2016.05.027","volume":"161","author":"SM Ayuk","year":"2016","unstructured":"Ayuk SM, Abrahamse H, Houreld NN. The role of photobiomodulation on gene expression of cell adhesion molecules in diabetic wounded fibroblasts in vitro. J Photochem Photobiol B. 2016;161:368\u201374.","journal-title":"J Photochem Photobiol B"},{"key":"2033_CR23","doi-asserted-by":"publisher","first-page":"9821","DOI":"10.1073\/pnas.93.18.9821","volume":"93","author":"JG Herman","year":"1996","unstructured":"Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A. 1996;93:9821\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2033_CR24","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnj004","volume":"34","author":"JD Nelson","year":"2006","unstructured":"Nelson JD, Denisenko O, Sova P, Bomsztyk K. Fast chromatin immunoprecipitation assay. Nucleic Acids Res. 2006;34:e2.","journal-title":"Nucleic Acids Res"},{"doi-asserted-by":"publisher","unstructured":"Alspach E, Stewart SA. RNA-binding protein immunoprecipitation (RIP) to examine AUF1 binding to senescence-associated secretory phenotype (SASP) factor mRNA. Bio Protoc. 2015;5.\u00a0https:\/\/doi.org\/10.21769\/BioProtoc.1481.","key":"2033_CR25","DOI":"10.21769\/BioProtoc.1481"},{"key":"2033_CR26","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/art.22427","volume":"56","author":"S Sahebjam","year":"2007","unstructured":"Sahebjam S, Khokha R, Mort JS. Increased collagen and aggrecan degradation with age in the joints of Timp3(\u2212\/\u2212) mice. Arthritis Rheum. 2007;56:905\u20139.","journal-title":"Arthritis Rheum"},{"key":"2033_CR27","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1002\/iub.1482","volume":"68","author":"J Shi","year":"2016","unstructured":"Shi J, Zhang C, Yi Z, Lan C. Explore the variation of MMP3, JNK, p38 MAPKs, and autophagy at the early stage of osteoarthritis. IUBMB Life. 2016;68:293\u2013302.","journal-title":"IUBMB Life"},{"key":"2033_CR28","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1089\/dna.2016.3397","volume":"35","author":"G Zhang","year":"2016","unstructured":"Zhang G, Wu Y, Xu D, Yan X. Long noncoding RNA UFC1 promotes proliferation of chondrocyte in osteoarthritis by acting as a sponge for miR-34a. DNA Cell Biol. 2016;35:691\u20135.","journal-title":"DNA Cell Biol"},{"key":"2033_CR29","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1089\/dna.2017.3678","volume":"36","author":"Y Li","year":"2017","unstructured":"Li Y, Li S, Luo Y, Liu Y, Yu N. LncRNA PVT1 regulates chondrocyte apoptosis in osteoarthritis by acting as a sponge for miR-488-3p. DNA Cell Biol. 2017;36:571\u201380.","journal-title":"DNA Cell Biol"},{"key":"2033_CR30","doi-asserted-by":"publisher","first-page":"8432","DOI":"10.1002\/jcb.27057","volume":"119","author":"Z Yang","year":"2018","unstructured":"Yang Z, Tang Y, Lu H, Shi B, Ye Y, Xu G, et al. Long non-coding RNA reprogramming (lncRNA-ROR) regulates cell apoptosis and autophagy in chondrocytes. J Cell Biochem. 2018;119:8432\u201340.","journal-title":"J Cell Biochem"},{"key":"2033_CR31","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.matbio.2010.10.007","volume":"30","author":"M Durigova","year":"2011","unstructured":"Durigova M, Nagase H, Mort JS, Roughley PJ. MMPs are less efficient than ADAMTS5 in cleaving aggrecan core protein. Matrix Biol. 2011;30:145\u201353.","journal-title":"Matrix Biol"},{"key":"2033_CR32","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1042\/BJ20100725","volume":"431","author":"NH Lim","year":"2010","unstructured":"Lim NH, Kashiwagi M, Visse R, Jones J, Enghild JJ, Brew K, et al. Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications. Biochem J. 2010;431:113\u201322.","journal-title":"Biochem J"},{"key":"2033_CR33","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1002\/art.24291","volume":"60","author":"AJ Pockert","year":"2009","unstructured":"Pockert AJ, Richardson SM, Le Maitre CL, Lyon M, Deakin JA, Buttle DJ, et al. Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration. Arthritis Rheum. 2009;60:482\u201391.","journal-title":"Arthritis Rheum"},{"key":"2033_CR34","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.matbio.2016.03.007","volume":"56","author":"K Yamamoto","year":"2016","unstructured":"Yamamoto K, Okano H, Miyagawa W, Visse R, Shitomi Y, Santamaria S, et al. MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1. Matrix Biol. 2016;56:57\u201373.","journal-title":"Matrix Biol"},{"key":"2033_CR35","doi-asserted-by":"publisher","first-page":"3776","DOI":"10.1002\/art.24074","volume":"58","author":"PL van Lent","year":"2008","unstructured":"van Lent PL, Grevers LC, Blom AB, Arntz OJ, van de Loo FA, van der Kraan P, et al. Stimulation of chondrocyte-mediated cartilage destruction by S100A8 in experimental murine arthritis. Arthritis Rheum. 2008;58:3776\u201387.","journal-title":"Arthritis Rheum"},{"key":"2033_CR36","doi-asserted-by":"publisher","first-page":"31","DOI":"10.22203\/eCM.v021a03","volume":"21","author":"M Durigova","year":"2011","unstructured":"Durigova M, Troeberg L, Nagase H, Roughley PJ, Mort JS. Involvement of ADAMTS5 and hyaluronidase in aggrecan degradation and release from OSM-stimulated cartilage. Eur Cells Materials. 2011;21:31\u201345.","journal-title":"Eur Cells Materials"},{"key":"2033_CR37","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1177\/147323000803600601","volume":"36","author":"K Huang","year":"2008","unstructured":"Huang K, Wu LD. Aggrecanase and aggrecan degradation in osteoarthritis: a review. J Int Medical Res. 2008;36:1149\u201360.","journal-title":"J Int Medical Res"},{"key":"2033_CR38","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1093\/nar\/26.12.2935","volume":"26","author":"AV Tinker","year":"1998","unstructured":"Tinker AV, Brown CJ. Induction of XIST expression from the human active X chromosome in mouse\/human somatic cell hybrids by DNA demethylation. Nucleic Acids Res. 1998;26:2935\u201340.","journal-title":"Nucleic Acids Res"},{"key":"2033_CR39","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nrg.2017.80","volume":"19","author":"F Lyko","year":"2018","unstructured":"Lyko F. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev Genet. 2018;19:81\u201392.","journal-title":"Nat Rev Genet"},{"key":"2033_CR40","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4419-9967-2_1","volume":"754","author":"B Jin","year":"2013","unstructured":"Jin B, Robertson KD. DNA methyltransferases, DNA damage repair, and cancer. Adv Exp Med Biol. 2013;754:3\u201329.","journal-title":"Adv Exp Med Biol"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-019-2033-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-019-2033-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-019-2033-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:57:00Z","timestamp":1607389020000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-019-2033-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["2033"],"URL":"https:\/\/doi.org\/10.1186\/s13075-019-2033-5","relation":{},"ISSN":["1478-6362"],"issn-type":[{"type":"electronic","value":"1478-6362"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"9 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The current study was approved by the Institutional Review Board of Yiwu Central Hospital, the Affiliated Yiwu Hospital of Wenzhou Medical University and conducted in strict accordance with <i>Declaration of Helsinki<\/i> (Clinical trial registration number: ChiCTR1900025348). Signed informed consents were obtained from all patients prior to the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"271"}}